News for the Multiple Sclerosis Community

Interferon Beta Responders and Non-Responders

I've wished someone would do a study like this for a while. We all know that interferons reduce relapses by about 30% in the group of people studied, but what does this mean to individuals? It seems clear (empirically) that some people respond well and some not at all. What's the difference between these groups.

This study looked at two hundred sixty-two patients with relapsing MS who received at least 6 months of IFNB: 200 relapsing remitting (RR) and 62 relapsing secondary progressive (SP). One-third of patients experienced a higher or identical annual relapse rate while on IFNB treatment. Compared with nonresponders, responders were older and had longer disease duration at the time IFNB was initiated. RRMS responders also had a higher relapse rate during the year prior to IFNB therapy and SPMS responders had a higher Disability Status Scale score at initiation of IFNB.

I think there may be a little "regression to the mean" going on there with the high-relapse subjects, but let's figure this out!

In my opinion, the results from this study don't mean very much. As Art mentions, there is definitely the risk of regression to the mean affecting the results. We all know that an individual's relapse rate can vary over time -- so how many people were classified as responders just because their relapse rate swung downward coincidentally with the start of IFN-b? Conversely, how many nonresponders happened to be at a low rate and then coincidentally swung upward after treatment start? The study also found that responders tended to be older and have longer disease duration, but relapse rate has been shown to decline with duration of disease, so perhaps many of these older, longer-term patients would have had fewer relapses anyway. The finding that longer disease durations are associated with response to IFN-b also seems to contradict the current push toward getting people on IFN-b early after diagnosis (or even after the first symptom), under the hypothesis that IFN-b is most effective early on when inflammation is most operative. Unfortunately, this interesting contradiction was not explored in the study discussion.

My other problem with this study is that it doesn't provide much to go on in terms of predicting who will respond to IFN-b. I think a better course of action is to study biological markers, gene variants, or other physiological evidence for correlations to treatment response or nonresponse. These types of studies are starting to be performed now with IFN-b (see this and this) and provide a much better chance of finding one or more factors (maybe a combination) that more clearly predict whether someone will respond to the treatment or not. Finding such factors would also provide more to go on in terms of understanding the drug's mechanism of action.